Effects of Long-term Norfloxacin Therapy in Patients With Advanced Cirrhosis.

BACKGROUND & AIMS: There is debate over the effects of long-term oral fluoroquinolone therapy in patients with advanced cirrhosis. We performed a randomized controlled trial to evaluate the effects of long-term treatment with the fluoroquinolone norfloxacin on survival of patients with cirrhosis. METHODS: We performed a double-blind trial of 291 patients with Child-Pugh class C cirrhosis who had not received recent fluoroquinolone therapy. The study was performed at 18 clinical sites in France from April 2010 through November 2014. Patients were randomly assigned to groups given 400 mg norfloxacin (n = 144) or placebo (n = 147) once daily for 6 months. Patients were evaluated monthly for the first 6 months and at 9 months and 12 months thereafter. The primary outcome was 6-month mortality, estimated by the Kaplan-Meier method, censoring spontaneous bacterial peritonitis, liver transplantation, or loss during follow-up. RESULTS: The Kaplan-Meier estimate for 6-month mortality was 14.8% for patients receiving norfloxacin and 19.7% for patients receiving placebo (P = .21). In competing risk analysis that took liver transplantation into account, the cumulative incidence of death at 6 months was significantly lower in the norfloxacin group than in the placebo group (subdistribution hazard ratio, 0.59; 95% confidence interval, 0.35-0.99). The subdistribution hazard ratio for death at 6 months with norfloxacin vs placebo was 0.35 (95% confidence interval, 0.13-0.93) in patients with ascites fluid protein concentrations <15 g/L and 1.39 (95% confidence interval, 0.42-4.57) in patients with ascites fluid protein concentrations ≥15 g/L. Norfloxacin significantly decreased the incidence of any and Gram-negative bacterial infections without increasing infections caused by Clostridium difficile or multiresistant bacteria. CONCLUSIONS: In a randomized controlled trial of patients with advanced cirrhosis without recent fluoroquinolone therapy, norfloxacin did not reduce 6-month mortality, estimated by the Kaplan-Meier method. Norfloxacin, however, appears to increase survival of patients with low ascites fluid protein concentrations. ClinicalTrials.gov ID: NCT01037959.

Effects of Age on Treatment of Chronic Hepatitis C with Direct Acting Antivirals.

INTRODUCTION AND AIM: Data on the efficacy and tolerance of interferon-free treatment in chronic hepatitis C (CHC) in elderly patients are limited in phase II-III trials. MATERIAL AND METHODS: A prospective cohort of adult patients with CHC treated in French general hospitals. RESULTS: Data from 1,123 patients, distributed into four age groups, were analyzed. Of these, 278 were > 64 years old (fourth quartile) and 133 were > 73 years old (tenth decile). Elderly patients weighed less, were more frequently treatment-experienced women infected with genotype 1b or 2, while they less frequently had genotype 3 or HIV coinfection, but had more frequent comorbidities and drug consumption. Half of the patients had cirrhosis, whatever their ages. The main treatment regimens were sofosbuvir/ledipasvir (37.8%), sofosbuvir/daclatasvir (31.8%), sofosbuvir/simeprevir (16.9%), sofosbuvir/ribavirin (7.8%); ribavirin was given to 24% of patients. The overall sustained virological response (SVR) rate was 91.0 % (95% CI: 89.292.5%) with no difference according to age. Logistic regression of the independent predictors of SVR were albumin, hepatocellular carcinoma and treatment regimen, but not age. The rate of severe adverse events (66 in 59/1062 [5.6%] patients) tended to be greater in patients older than 64 years of age (21/261,8.1%), but the only independent predictors of SAE by logistic regression were cirrhosis and baseline hemoglobin. Patient-reported overall tolerance was excellent in all age groups, and patient-reported fatigue decreased during and after treatment, independent of age. CONCLUSIONS: The high efficacy and tolerance of interferon-free regimens is confirmed in elderly patients in real-life conditions.

Features of Autoimmune Pancreatitis Associated With Inflammatory Bowel Diseases.

BACKGROUND & AIMS: Few people know of autoimmune pancreatitis (AIP), a rare disorder associated with inflammatory bowel diseases (IBD). We aimed to describe phenotype and outcomes of IBD and AIP when associated. METHODS: We performed a retrospective study of cases of AIP in IBD identified from the multicenter Groupe d'Etude Thérapeutique des Affections Inflammatoires du tube Digestif in Belgium and France from July 2012 through July 2015. Patients were diagnosed with AIP based on the International Consensus Diagnostic Criteria for AIP. A definitive AIP diagnosis was based on histological analysis of pancreatic resection specimens or samples collected by fine-needle aspiration during endoscopic ultrasound. Patients with probable type 1 AIP were identified based on imaging findings, clinical and/or radiologic responses to steroids, level of serum immunoglobulin G4, and involvement of other organs. Patients with probable type 2 AIP were identified based on imaging findings, clinical and/or radiologic responses to steroids, and association with IBD. The primary objective was to collect information on the characteristics of AIP in patients with IBD. We also compared features of patients with IBD with and without AIP in a case-control analysis, using multivariate analysis. RESULTS: We analyzed data from 91 individuals with AIP and IBD (47 women) seen at 23 centers (58 had ulcerative colitis [UC] and 33 Crohn's disease [CD]). Eighty-nine patients had type 2 AIP, and 2 patients had type 1 AIP. The mean age at diagnosis of AIP was 35 ± 12 years, and for IBD it was 32 ± 12 years. AIP preceded IBD in 19 patients (21%). Over a mean follow-up period of 5.7 ± 4.9 years, 31 patients (34%) relapsed, 11 patients (12%) developed diabetes, and 17 patients (19%) developed exocrine pancreatic insufficiency. In patients with UC, factors independently associated with AIP included proctitis (odds ratio [OR], 2.9; 95% confidence interval [CI], 1.3-6.3; P = .007) and colectomy (OR, 7.1; 95% CI, 2.5-20; P = .0003). In patients with CD, AIP was significantly associated with fewer perianal lesions (OR, 0.16; 95% CI, 0.03-0.77; P = .023), non-stricturing non-penetrating CD (OR, 6.7; 95% CI, 1.25-33.3; P = .0029), and higher rate of colectomy (OR, 27.8; 95% CI, 3.6-217; P = .0029). CONCLUSIONS: In a multicenter retrospective analysis of patients with AIP and IBD, followed for an average of 5.7 ± 4.9 years, we found most to have type 2 AIP. Two-thirds of patients have UC, often with proctitis. One-third of patients have CD, often with inflammatory features. Patients with IBD and AIP have higher rates of colectomy than patients with just IBD.

Cirrhotic patients with portal hypertension-related bleeding and an indication for early-TIPS: a large multicentre audit with real-life results.

BACKGROUND: The Baveno VI consensus meeting concluded that an early TIPS must be considered in high-risk cirrhotic patients presenting with variceal bleeding (VB) (Child B + active bleeding at endoscopy or Child C10-13 patients). Whether this therapeutic approach is feasible in a real-life setting remains unclear. AIMS: To determine (1) the proportion of patients eligible for early-TIPS among cirrhotic patients with VB, (2) the proportion of these patients who underwent early-TIPS placement and the main reasons for discarding TIPS, and (3) the outcomes of patients who experienced early-TIPS placement in a large, national, prospective, multicentre audit including academic and non-academic centres. MATERIALS AND METHODS: All French centres recruiting gastrointestinal bleeding were invited to participate. All consecutive patients with cirrhosis and PHT-related bleeding were included. RESULTS: 964 patients were included (58 centres: 26 academic, 32 non-academic; patient characteristics: male sex, 77%; age, 59.6 ± 12.1 years; aetiologies of cirrhosis (alcoholic,viral/other, 67%/15%/18%); source of bleeding (EV/GV/other, 80/11/9%); active bleeding at endoscopy 34%; Child A 21%/B 44%/C 35%. Overall, 35% of the patients were eligible for early-TIPS, but only 6.8%, displaying less severe cirrhosis underwent early-TIPS placement. The main reason for discarding TIPS was a lack of availability. The actuarial probability of survival at one year was significantly increased in early-TIPS patients (85.7±0.07% vs 58.9±0.03%, p=0.04). The severity of liver disease was the only parameter independently associated with improved one-year survival. CONCLUSION: In this real-life study, one-third of the cirrhotic patients admitted for VB fulfilled the criteria for early-TIPS placement, whereas only 7% had access to TIPS. TIPS was restricted to patients displaying less severe cirrhosis. The severity of liver disease was the only parameter that influenced survival.

Albumin Use in Patients With Cirrhosis in France: Results of the "ALBU-LIVE" Survey: A Case for Better EASL Guidelines Diffusion and/or Revision.

INTRODUCTION: The use of human albumin for the management of cirrhosis has increased. Recommendations have been published for therapeutic paracentesis (TP), spontaneous bacterial peritonitis (SBP), and type 1 hepatorenal syndrome (HRS). The goal of this survey was to assess the prescription practices of French hepatogastroenterologists. METHODS: All hepatogastroenterologists were contacted. The questionnaire evaluated (1) the use of albumin in validated indications and (2) the prescription of albumin for nonvalidated clinical situations. RESULTS: Responses were analyzed from 451 (50.1%) practitioners. The mean age was 40 years (range, 24 to 67 y). Physicians practiced in a university hospital (47.7%) or a general hospital (45.8%). There were 56.7% senior practitioners. Overall 99.6% of the practitioners compensated for TP. Albumin was used by 87.8% of the physicians, with a fixed dose being used by 84.6%. For SBP, 94% of the physicians used albumin concomitantly with antibiotics. The recommended protocol was followed by 56.2% of the practitioners: more often by senior university hospital practitioners than by senior general hospital practitioners (P=0.015). About 66.5% used albumin infusion for the diagnosis of HRS: used more often by senior university hospital practitioners (P=0.0006). Albumin was used concomitantly with vasopressor treatment by 84%; the dose and the duration varied considerably. About 23.5% used albumin for severe bacterial infection, 47.9% for severe hyponatremia, 43.9% for severe hypoalbuminemia, and 65.9% for hydrothorax. CONCLUSIONS: In this large French survey, albumin is only prescribed in accordance with recommendations for TP. The schedule for SBP is followed by only 56% of the practitioners. The use of albumin for HRS is not adapted to recommendations, which are not well known, suggesting that they should be more diffused.

The Periscreen Strip Is Highly Efficient for the Exclusion of Spontaneous Bacterial Peritonitis in Cirrhotic Outpatients.

OBJECTIVES: We aimed to assess the performance of a new strip (Periscreen) for the rapid diagnosis of spontaneous bacterial peritonitis (SBP). METHODS: Ascitic fluid (AF) of cirrhotic patients hospitalized between March 2014 and August 2015 was independently tested by two readers using the new strip, which has four colorimetric graduations (negative, trace, small, and large). SBP was diagnosed on neutrophils in ascites>250/mm3. Ascites not related to portal hypertension were excluded. RESULTS: Overall, 649 patients from 21 French centers were included and 1,402 AF (803 AF samples from 315 outpatients and 599 samples from 334 inpatients) were assessed. Eighty-four AF samples (17 AF in 9 outpatients and 67 AF in 31 inpatients) were diagnosed as SBP. The prevalence of SBP was 6% (2.1% in outpatients vs. 11.2% in inpatients; P<0.001) and 7.2% in patients with symptoms suggestive of SBP (3% in outpatients vs. 11.3% in inpatients; P<0.001). The κ value for inter-reader agreement was 0.81 (95% confidence interval: 0.77-0.84) when using the "trace" threshold. Considering discordant results (n=131) as positive to interpret the diagnostic performance of the strip at the "trace" threshold, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 91.7, 57.1, 12.0, and 99.1%, respectively. At this "trace" threshold, sensitivity and NPV were both 100% in outpatients, and 89.5 and 97.9% in inpatients, respectively. At the "small" threshold, sensitivity, specificity, PPV and NPV were 81.0, 85.9, 25.9 and 98.7%, respectively. CONCLUSIONS: The Periscreen strip is a rapid and highly efficient tool for excluding SBP in the outpatient setting.

Effectiveness and Safety of Tenofovir Disoproxil Fumarate in Chronic Hepatitis B: A 3-Year, Prospective, Real-World Study in France.

BACKGROUND AND AIMS: Tenofovir disoproxil fumarate (TDF) demonstrated potent and sustainable antiviral efficacy and a good safety profile in patients with chronic hepatitis B (CHB) in controlled clinical trials. Real-world data are important to confirm effectiveness and safety data in patient populations encountered in routine clinical practice. METHODS: This non-interventional, prospective, 36-month study included treatment-naïve and treatment-experienced patients with CHB initiating their first TDF regimen (monotherapy or combination therapy) in routine clinical practice in France. Clinical, virologic, biochemical, compliance, and safety data were collected. RESULTS: Data from 440 consecutive patients from 58 centers were analyzed. The majority of the cohort was male (71 %), hepatitis B "e" antigen-negative (HBeAg-) (74 %), and treatment-experienced (56 %); 11 % were aged ≥65 years; and comorbidities were reported in 39 %. After 12 months, 92 % of the overall cohort achieved virologic response (HBV DNA <69 IU/mL) which was maintained to 36 months (96 %); virologic response was achieved by >90 % of patients irrespective of HBeAg status, age, or prior treatment history. At 36 months, 77 % of patients had normal alanine aminotransferase levels. Fourteen patients lost hepatis B surface (HBs) antigen, and seven seroconverted to anti-HBs. TDF was well tolerated over the 36-month study, including in 14 women who became pregnant during the study. Median estimated glomerular filtration rate did not change markedly from baseline irrespective of prior treatment history. CONCLUSIONS: TDF demonstrated potent virologic and biochemical responses across a broad range of patients reflective of routine clinical practice. The safety profile was consistent with results from pivotal trials.

A French national survey on the use of antibiotic prophylaxis in cirrhotic patients.

BACKGROUND: Guidelines recommend antibiotic prophylaxis (AP) in well-selected groups of cirrhotic patients, but the impact of these recommendations has not been assessed in France. AIM: To evaluate AP prescription tendencies for gastrointestinal bleeding, and primary and secondary prophylaxis of spontaneous bacterial peritonitis (SBP). METHODS: Practitioners (n = 1,159) working in general hospitals (GH) or in university hospitals (UH) received a self-administered questionnaire. RESULTS: Three hundred and eighty-nine (33.6%; GH 35% and UH 30.4%) practitioners responded. AP was prescribed by 97.7%, 72.3% and 94.8% of practitioners, without significant differences between UH and GH, respectively, for gastrointestinal bleeding (quinolones 48.2%, third-generation cephalosporins 27.7% and amoxicillin-clavulanic acid 22.2%), primary (quinolones 97.2%) and secondary prophylaxis of SBP (quinolones 99%). For gastrointestinal bleeding, ofloxacin (47.6%) and norfloxacin (37.4%) were the main quinolones prescribed, and ceftriaxone (77%) was the main third-generation cephalosporin prescribed. The principal reasons for prescribing AP were a decrease in bacterial infection (88.9% for gastrointestinal bleeding, 91.3% for primary and 94.3% for secondary prophylaxis of SBP), a recommendation by a consensus conference (83%, 38% and 74.4% respectively) and an improvement in survival (72.8%, 41.3% and 57.7% respectively). Only 31.7% of practitioners (39.6% for UH vs. 28.6% for GH; P = 0.038) believed that AP may reduce the risk of bleeding recurrence. Reported side effects (28%) of AP mainly concerned the risk of quinolone resistance (62% of cases). CONCLUSION: Antibiotic prophylaxis is well-recognized by French practitioners, but its routine use depends on the expertise of practitioners. Quinolones remain the main antibiotic class prescribed irrespective of the type of prophylaxis.

Outcomes of upper gastrointestinal bleeding are similar between direct oral anticoagulants and vitamin K antagonists.

BACKGROUND: The increased risk of upper gastrointestinal bleeding (UGIB) related to direct oral anticoagulants (DOACs) as compared to vitamin K antagonists (VKA) remains debated. AIMS: To describe the epidemiology and outcomes of UGIB in patients treated with oral anticoagulants. METHODS: A prospective, multicentre study in French general hospitals enrolled all consecutive patients with UGIB during one year. Patients treated with oral anticoagulants were retrieved from the cohort. Main outcomes were mortality and rebleeding during the first 6 weeks and need for non-endoscopic treatment (surgery or interventional radiology). RESULTS: Among the 2498 patients included, 475 (19%) had an oral anticoagulant, mostly with VKA (267 patients [56.2%]). Baseline characteristics were similar between the groups except for renal failure and cirrhosis that were more prevalent in the VKA group. Gastroscopy was normal in 73 patients (15.3%); peptic lesions were the main cause of UGIB (n = 233, 49%). Endoscopic treatment was performed in 128 patients (26.9%), leading to bleeding resolution in 74% (n = 95). Mortality rate at 6 weeks was 12.4% (59 patients), and was higher in the VKA group compared to DOACs (16.1% vs 7.8%, P < 0.01). By multivariate analysis, only the Charlson index ≥ 5 and UGIB occurrring in in-patients were independently associated with mortality. Rebleeding (56 patients [11.8%]) and need for non-endoscopic treatment (18 patients [3.8%]) were not associated with the type of anticoagulant. CONCLUSION: DOACs do not alter outcomes of UGIB as compared to VKA. Comorbidities and associated treatment are the most important factors worsening the prognosis of UGIB.

Hepatitis C treatment with all-oral direct-acting antivirals: Effectiveness and tolerance in a multicenter, prospective, observational study from French general hospitals (APROVVIE, ANGH).

BACKGROUND AND AIMS: According to clinical trials, the treatment of patients with chronic hepatitis C (CHC) with second-generation direct acting antiviral agents (DAAs) is highly efficient and well tolerated. The goal of this study was to investigate the effectiveness and safety of various combinations of these drugs during their first 2 years of use in the real-world practice of French general hospitals. METHODS: Data from patients treated with all-oral DAAs in 24 French non-academic hospital centers from March 1, 2014 to January 1, 2016, were prospectively recorded. The sustained virological response 12-24 weeks after treatment (SVR 12-24) was estimated and severe adverse events (SAE) were evaluated and their predictive factors were determined using logistic regression. RESULTS: Data from 1123 patients were analyzed. The population was 69% genotype (G) 1, 13% G3, 11.5% G4, 5% G2, 49% with cirrhosis and 55% treatment-experienced. The treatment regimens were sofosbuvir/ledipasvir (38%), sofosbuvir/daclatasvir (32%), sofosbuvir/simeprevir (17%), ombitasvir+paritaprevir+ritonavir (5%) (with dasabuvir 3.5%), and sofosbuvir/ribavirin (8%). Ribavirin was given to 24% of patients. The SVR 12-24 was 91.0% (95% CI: 89.2-92.5%). Sofosbuvir-ribavirin was less effective than other regimens. The independent predictors of SVR 12-24 by logistic regression were body weight, albumin, previous hepatocellular carcinoma and treatment regimen (sofosbuvir/ribavirin vs. others). Sixty-four severe adverse events (SAE) were observed in 59 [5.6%] patients, and were independently predicted by cirrhosis and baseline hemoglobin. Serum creatinine increased during treatment (mean 8.5%, [P<10-5]), satisfying criteria for acute kidney injury in 62 patients (7.3%). Patient-reported overall tolerance was excellent, and patient-reported fatigue decreased during and after treatment. CONCLUSIONS: Second generation DAAs combinations are as effective and well tolerated in a « real-world ¼ population as in clinical trials. Further studies are needed on renal tolerance.

Prevalence of hepatitis C infection and risk factors in hospitalized diabetic patients: results of a cross-sectional study.

OBJECTIVES: Although there may exist a nosocomial risk of hepatitis C virus (HCV) infection in patients with type 1 or type 2 diabetes, this risk has not been fully investigated thus far and its magnitude is unknown. The aim of this multicenter cross-sectional study was to evaluate the prevalence of, and risk factors for, hepatitis C infection in consecutive hospitalized patients with diabetes and to assess the nosocomial risk and magnitude of HCV infection in these patients. PATIENTS AND METHODS: Consecutive hospitalized patients with diabetes seen in 11 French hepatogastroenterology and diabetology departments were studied. The prevalence of anti-HCV antibodies was compared with that observed in healthy blood donors and individuals seen during routine medical checkup. Diabetic patients with anti-HCV antibodies were compared with patients without anti-HCV antibodies for assessment of risk factors. RESULTS: In total 1561 patients were studied. Independent risk factors for HCV infection were assessed through multivariate analysis. Thirty-three patients (2.11%) had anti-HCV antibodies and 21 (63.70%) had HCV identified risk factors. The prevalence of HCV infection was higher in patients with diabetes than in blood donors (0.08%) or healthy controls (0.20%) (P<0.001). Multivariate analysis identified four independent risk factors for HCV infection: blood transfusion before 1991 [odds ratio (OR)=2.88, P=0.033], intravenous drug use (OR=21.37, P=0.012), treatment in a hepatogastroenterology center (OR=4.17, P=0.002) and a high number (>2) of previous admissions since the onset of diabetes (OR=2.52, P=0.039). CONCLUSION: A nosocomial source of HCV infection in hospitalized diabetic patients is suggested by the increased risk of HCV infection associated with the number of hospitalizations. This may account for at least 36% of cases of HCV infection.

Management of gastric varices: a French national survey.

BACKGROUND AND AIMS: Bleeding from gastric varices is more severe than that from esophageal varices, but its management remains debated. We aimed to determine how French hepatogastroenterologists manage cirrhotic patients with gastric varices. METHODS: Hepatogastroenterologists (n=1163) working in general or university hospitals received a self-administered questionnaire. RESULTS: Overall, 155 hepatogastroenterologists (13.3%) from 112 centers (33.3%; 39/40 university hospitals, 73/296 general hospitals) answered. Primary prophylaxis was used by 98.1% of hepatogastroenterologists as follows: ß-blockers 96.1% (93.8 vs. 97.0%; university vs. general hospitals respectively; P=0.57), glue obliteration 16.9% (17.2 vs. 16.3%; P=0.88), and transjugular intrahepatic portosystemic shunt (TIPS) 8.0% (12.7 vs. 4.6%; P=0.12). To manage bleeding, university hospitals had greater local access to glue obliteration (95.4 vs. 68.2%; P<0.001) and TIPS (78.5 vs. 3.5%; P<0.001). Early TIPS was proposed by 53.6% (72.1 vs. 39.2%; P<0.001). Glue obliteration was performed under general anesthesia (86.1%) using Glubran (43.1%) or Histoacryl (52.9%), and lipiodol (78.8%) with varying degrees of dilution (1 : 10 to 3 : 4). The injected volume per varix varied widely (1-20 ml). Glue obliteration, band ligation, or both were used by, respectively, 64.2, 18.2, and 17.5% of practitioners. Almost all hepatogastroenterologists (98%) performed secondary prophylaxis: ß-blockers 74.7% (75.0 vs. 74.4%, university vs. general hospitals; P=0.93), glue obliteration 66.0% (76.9 vs. 57.6%; P=0.013), and TIPS 30.0% (39.1 vs. 23.3%; P=0.037). CONCLUSION: The management of gastric varices in France is heterogeneous across centers. University hospitals have better access to techniques such as glue obliteration and TIPS. As bleeding from gastric varices has a poor outcome, guidelines should be established to standardize clinical practices and design further studies.

[Acute pancreatitis revealing Behçet disease]. / Pancréatite aiguë révélant une maladie de Behçet.

We report here a case of acute pancreatitis revealing Behcet's disease in an 18-year-old woman. Pancreatitis was due to ischemia secondary to severe abnormalities of the celiac trunk arteries with pseudo-aneurysms. The outcome was favourable after the administration of corticosteroids and cyclophosphamide. The patient did not experience relapse of pancreatitis 2 years after diagnosis.

Usefulness of routine analysis of ascitic fluid at the time of therapeutic paracentesis in asymptomatic outpatients. Results of a multicenter prospective study.

AIM: The guidelines of the American Association for the Study of Liver Diseases recommend performing exploratory paracentesis on each patient with cirrhosis and chronic ascites. The aim of the study was to evaluate the prevalence of spontaneous bacterial peritonitis and culture-negative neutrocytic ascites in a large population of consecutive asymptomatic cirrhotic ascitic ambulatory patients. METHODS: Patients with cirrhosis and tense ascites hospitalized from January to September 2000 in 5 hepatogastroenterology units prospectively underwent an exploratory paracentesis with cytobacteriological, biochemical and bedside inoculation into aerobic and anaerobic blood culture bottles. Patients studied were not receiving antibiotics except for norfloxacin and had no obvious sign of infection such as fever or hypothermia, chills, unusual abdominal tenderness, de novo or worsening hepatic encephalopathy, recent gastrointestinal bleeding, acute renal failure or marked arterial hypotension. Clinical and biological findings and ascitic fluid cytological and bacteriological results were evaluated at each exploratory paracentesis. The results are given in mean +/- standards deviations with range. RESULTS: Sixty-seven cirrhotic patients (48M/19F, mean age 59 +/- 9 years) had 270 therapeutic paracenteses, preceded by an exploratory aspiration. Fifty-nine patients (88%) had alcoholic cirrhosis. Twenty-five patients (37.3%) received norfloxacin. At first paracentesis 41 (61.2%) and 26 (38.8%) patients were class B and C respectively according to the Child-Pugh classification; the mean Child-Pugh score was 9 +/- 1.5. None had suspicion of infection. The mean number of paracenteses was 5 +/- 4.3 per patient; 59.6% of the paracenteses (161) were compensated with human albumin. Ascitic protein concentration was 17.5 +/- 8.6 g/l, ascitic fluid cell count and number of neutrophils were 127 +/- 155/mm3 and 5.9 +/- 14/mm3 (0-60), respectively. No patient had spontaneous bacterial peritonitis nor culture-negative neutrocytic ascites; 10 cases of monomicrobial bacterascites were observed, all with commensal germs. CONCLUSIONS: In the absence of obvious signs of infection, the prevalence of spontaneous bacterial peritonitis and culture-negative neutrocytic ascites in asymptomatic cirrhotic outpatients with ascites is near 0%. Moreover, for 100 large volume paracenteses, not performing exploratory paracentesis corresponds to a savings of 5,500 euros, without risk for these patients.

Effects of ursodeoxycholic acid (ursodiol) treatment on chronic viral hepatitis in heart transplant patients: results of a prospective, double-blind, placebo-randomized study.

BACKGROUND: Chronic viral hepatitis averages 15% to 20% in heart transplant patients. Several studies have shown that ursodiol may improve liver biochemistry in patients with chronic hepatitis. We used a double-blind randomized controlled trial to evaluate the effect of ursodiol in heart transplant patients with chronic viral hepatitis. METHODS: Thirty heart patients with chronic viral hepatitis B, C, or non-A-G received ursodiol, 800 mg per day (group 1), and 30 received placebo (group 2) for 12 months. Endpoints were improvement in liver biochemical tests and in total Knodell score. Intent-to-treat and per-protocol analyses were performed. RESULTS: At entry, both groups were comparable for all of the studied parameters. During the study period, serum alanine aminotransferase, aspartate aminotransferase, and gamma-glutamyl transpeptidase variations were not different between group 1 and group 2 patients. Knodell score improved in 20% of group 1 patients and in 43% of group 2 patients (NS). Adverse events or mortality were not different in the two groups during the study period. Similar results were observed by intent-to-treat and per-protocol analyses. CONCLUSIONS: A 12-month course of ursodiol therapy had no effect on liver enzymes or liver histology in heart transplant patients with chronic hepatitis.

Low incidence of spontaneous bacterial peritonitis in asymptomatic cirrhotic outpatients.

AIM: To compare the incidence of spontaneous bacterial peritonitis in cirrhotic outpatients and inpatients undergoing therapeutic paracentesis METHODS: From January 1 to May 31, 2004, 1041 patients from 70 different hospitals underwent 2123 therapeutic abdominal paracentesis (AP) performed as a outpatient procedure in 355 and as inpatient procedure in 686 cases respectively. The following parameters were compared prospectively between outpatients and inpatients: spontaneous bacterial peritonitis (SBP) prevalence, age, gender, cause of cirrhosis, symptoms, score and grade according to Child-Pugh classification, cirrhosis complications, antibiotics treatment, serum creatinine, platelet count and ascitic protein concentration. RESULTS: SBP was observed in 91 patients. In the whole population the SBP prevalence was 8.7% (95%CI: 7.2-10.6) it was 11.7% (95%CI: 9.5-14.3) in inpatients and 3.1% (95%CI: 1.7-5.5) in outpatients (P < 0.00001). SBP prevalence was 8.3% (95%CI: 4.3-15.6) in symptomatic outpatients vs 1.2% (95%CI: 0.4-3.4) in asymptomatic outpatients (P < 0.002). Patients undergoing outpatient AP were significantly different from those undergoing inpatient AP; they were older (61.1 ± 11.1 years vs 59.4 ± 11.7 years; P = 0.028), cause of cirrhosis was less often alcohol (83 .7 vs 88.2%; P < 0.001), Child-Pugh score was lower (8.9 vs 10.1; P < 0.001) and more often B than C (63.7% vs 38%; P < 0.001). In addition, in outpatients the platelet count was higher (161 ± 93 Giga/L vs 143 ± 89 Giga/L; P = 0.003), serum total bilirubin concentration was lower (38.2 ± 60.7 µmol/L vs 96.3 ± 143.3 µmol/L; P < 0.0001), and ascitic protein concentration higher (17.9 ± 10.7 g/L vs 14.5 ± 10.9 g/L; P < 0.001) than in inpatients. CONCLUSION: In asymptomatic cirrhotic outpatients, the incidence of spontaneous bacterial peritonitis is low thus exploratory paracentesis could be avoided in these patients without significant risk.

Diagnostic accuracy of the Multistix 8 SG reagent strip in diagnosis of spontaneous bacterial peritonitis.

UNLABELLED: Recent studies have shown that the diagnosis of spontaneous bacterial peritonitis (SBP) can be rapidly obtained using leukocyte esterase reagent strips. However, published studies were restricted to one or two centers, and the number of patients with SBP was thus limited. The aims of the current prospective multicenter study were: (1) to assess the diagnostic accuracy of the Multistix 8SG urine test for the diagnosis of SBP; and (2) to assess the prevalence of SBP. From January to May 2004, 2 reactive strips were tested independently in inpatients with cirrhosis and in outpatients undergoing paracentesis. Cultures of ascitic fluid were performed at the bedside using aerobic and anaerobic blood culture bottles. Two thousand one hundred twenty-three paracenteses were performed in 1,041 patients from 70 centers. One hundred seventeen samples, obtained from 91 patients, had ascites polymorphonuclear cell (PMN) counts>or=250/microl (range, 250-34,000), among which 56 were associated with positive ascitic fluid cultures. The prevalence of SBP was 5.5% in the whole population, 9% in inpatients, and 1.3% in outpatients (P<0.0001). The prevalence of SBP was 0.57% in asymptomatic outpatients versus 2.4% in symptomatic outpatients (P=0.04). Using a threshold of 2+ for positivity of the reagent strip, sensitivity was 45.3% for the diagnosis of SBP, specificity was 99.2%, positive predictive value was 77.9%, and negative predictive value was 96.9%. CONCLUSION: This study confirms the low prevalence of SBP in asymptomatic outpatients according to a priori defined criteria, and indicates an absence of diagnostic efficacy for this specific strip test.